scholarly journals A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

2014 ◽  
Vol 307 (4) ◽  
pp. C338-C348 ◽  
Author(s):  
Hongguang Wei ◽  
J.-P. Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Wild Type ◽  
Leukemia Inhibitory Factor Receptor ◽  
Cell Width ◽  
Potent Effect ◽  
Western Blots ◽  
Adrenergic Response

We previously reported a point mutation substituting Cys for Arg111 in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825–13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806–27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca2+ transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes.

scholarly journals NH2-terminal truncations of cardiac troponin I and cardiac troponin T produce distinct effects on contractility and calcium homeostasis in adult cardiomyocytes

2015 ◽  
Vol 308 (5) ◽  
pp. C397-C404 ◽  
Author(s):  
Hongguang Wei ◽  
J.-P. Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Molecular Conformation ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Terminal Region ◽  
Cardiac Troponin T ◽  
Wild Type ◽  
Regulatory Structure ◽  
Ejection Time

Cardiac troponin I (TnI) has an NH2-terminal extension that is an adult heart-specific regulatory structure. Restrictive proteolytic truncation of the NH2-terminal extension of cardiac TnI occurs in normal hearts and is upregulated in cardiac adaptation to hemodynamic stress or β-adrenergic deficiency. NH2-terminal truncated cardiac TnI (cTnI-ND) alters the conformation of the core structure of cardiac TnI similarly to that produced by PKA phosphorylation of Ser23/24 in the NH2-terminal extension. At organ level, cTnI-ND enhances ventricular diastolic function. The NH2-terminal region of cardiac troponin T (TnT) is another regulatory structure that can be selectively cleaved via restrictive proteolysis. Structural variations in the NH2-terminal region of TnT also alter the molecular conformation and function. Transgenic mouse hearts expressing NH2-terminal truncated cardiac TnT (cTnT-ND) showed slower contractile velocity to prolong ventricular rapid-ejection time, resulting in higher stroke volume. Our present study compared the effects of cTnI-ND and cTnT-ND in cardiomyocytes isolated from transgenic mice on cellular morphology, contractility, and calcium kinetics. Resting cTnI-ND, but not cTnT-ND, cardiomyocytes had shorter length than wild-type cells with no change in sarcomere length. cTnI-ND, but not cTnT-ND, cardiomyocytes produced higher contractile amplitude and faster shortening and relengthening velocities in the absence of external load than wild-type controls. Although the baseline and peak levels of cytosolic Ca2+ were not changed, Ca2+ resequestration was faster in both cTnI-ND and cTnT-ND cardiomyocytes than in wild-type control. The distinct effects of cTnI-ND and cTnT-ND demonstrate their roles in selectively modulating diastolic or systolic functions of the heart.

scholarly journals Clinical Evaluation of the ACS:180 Cardiac Troponin I Assay

2001 ◽  
Vol 38 (5) ◽  
pp. 509-519 ◽  
Author(s):  
Paul O Collinson ◽  
Nigel Wiggins ◽  
David C Gaze
Keyword(s):  
Endurance Training ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Training Group ◽  
Storage Conditions ◽  
Cardiac Troponin I ◽  
Admission Diagnosis ◽  
Coronary Syndromes ◽  
Analytical Imprecision

All patients admitted to the coronary care unit with suspected acute coronary syndromes were evaluated by serial electrocardiography and blood draws on admission and at 4 and 12h from admission. Diagnosis was based on conventional WHO criteria. Samples were measured for creatine kinase (CK), cardiac troponin T (cTnT), myoglobin, CK isoenzyme MB (CK-MB) and cardiac troponin I (cTnI). A set of samples from individuals undergoing extreme endurance training was also examined. Analytical imprecision was consistent with published quality goals. Samples were stable for cTnI under a range of storage conditions, including multiple freeze-thaw cycles. CK-MB, cTnI and cTnT were equally efficient for the diagnosis of acute myocardial infarction, irrespective of the final diagnostic criteria used. Both cTnI and cTnT were of equal efficiency in the identification of a high-risk subgroup of patients with unstable angina. Significant elevations of cTnI were not seen in an endurance-training group.

Patterns and Diagnostic Value of Cardiac Troponin I vs. Troponin T and CKMB after OPCAB Surgery*

2001 ◽  
Vol 49 (3) ◽  
pp. 137-143 ◽  
Author(s):  
A. A. Peivandi ◽  
M. Dahm ◽  
U. Hake ◽  
G. Hafner ◽  
U. T. Opfermann ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Diagnostic Value ◽  
Cardiac Troponin I ◽  
Opcab Surgery

scholarly journals Biological variation of cardiac troponins in chronic kidney disease

2020 ◽  
Vol 57 (2) ◽  
pp. 162-169
Author(s):  
RA Jones ◽  
J Barratt ◽  
EA Brettell ◽  
P Cockwell ◽  
RN Dalton ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Biological Variation ◽  
Cardiac Troponin I ◽  
Cardiac Troponin T ◽  
Reference Change Value

Background Patients with chronic kidney disease often have increased plasma cardiac troponin concentration in the absence of myocardial infarction. Incidence of myocardial infarction is high in this population, and diagnosis, particularly of non ST-segment elevation myocardial infarction (NSTEMI), is challenging. Knowledge of biological variation aids understanding of serial cardiac troponin measurements and could improve interpretation in clinical practice. The National Academy of Clinical Biochemistry (NACB) recommended the use of a 20% reference change value in patients with kidney failure. The aim of this study was to calculate the biological variation of cardiac troponin I and cardiac troponin T in patients with moderate chronic kidney disease (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m2). Methods and results Plasma samples were obtained from 20 patients (median GFR 43.0 mL/min/1.73 m2) once a week for four consecutive weeks. Cardiac troponin I (Abbott ARCHITECT® i2000SR, median 4.3 ng/L, upper 99th percentile of reference population 26.2 ng/L) and cardiac troponin T (Roche Cobas® e601, median 11.8 ng/L, upper 99th percentile of reference population 14 ng/L) were measured in duplicate using high-sensitivity assays. After outlier removal and log transformation, 18 patients’ data were subject to ANOVA, and within-subject (CVI), between-subject (CVG) and analytical (CVA) variation calculated. Variation for cardiac troponin I was 15.0%, 105.6%, 8.3%, respectively, and for cardiac troponin T 7.4%, 78.4%, 3.1%, respectively. Reference change values for increasing and decreasing troponin concentrations were +60%/–38% for cardiac troponin I and +25%/–20% for cardiac troponin T. Conclusions The observed reference change value for cardiac troponin T is broadly compatible with the NACB recommendation, but for cardiac troponin I, larger changes are required to define significant change. The incorporation of separate RCVs for cardiac troponin I and cardiac troponin T, and separate RCVs for rising and falling concentrations of cardiac troponin, should be considered when developing guidance for interpretation of sequential cardiac troponin measurements.

Reply: The complementary role of cardiac troponin I and cardiac troponin T

2020 ◽  
Vol 78 ◽  
pp. 42
Author(s):  
Sjur H. Tveit ◽  
Peder L. Myhre ◽  
Helge Røsjø ◽  
Torbjørn Omland
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Cardiac Troponin T ◽  
Complementary Role
Sign in / Sign up

Export Citation Format

Share Document